Orthopaedic extremity injuries present a large medical and financial burden to both the United States and worldwide communities. Approximately 8 million bone fractures are reported per annum in the United States, and about 10% of these fractures do not heal properly. For injuries that involve a significant disturbance to the vascular supply, the rates of aberrant bone healing are nearly 50%. The most common complication is bony non-union. These non-unions can be very costly because of both the direct cost to revise as well as associated costs such as lost productivity due to absence from work. It has been estimated that these costs can be reduced by at least 50% if complications associated within the early healing can be avoided or addressed.
The most common treatment for non-unions is additional surgery. The clinical outcome of these procedures is negatively correlated to the time between the initial surgery and the second surgery due to the temporal course of fibrous tissue accumulation at the fracture site. Thus, there is a crucial clinical need to determine the course of bone healing (aberrant versus normal) in the vitally important early stages of fracture site treatment and management. Current strategies that utilize injections of osseous “biologic” therapeutics, bone morphogenetic proteins (BMPs) or other growth factors that potentiate the osteoinductive activities of BMPs, have been proposed for non-invasively treating bony non-unions in the early healing phase. However, the ability to diagnose if adjunctive biologic treatments are necessary is not currently available.
Though the exact mechanism through which the bone healing sequence becomes impaired is poorly understood, many of these non-unions or pseudoarthroses (fibrous unions) result when there is a fracture condition that does not proceed through a stabilized, direct bony bridging (intramembranous ossification) healing pathway. Currently, clinicians usually monitor healing visually by radiographs, and may examine the mechanical condition of the union via manually bending the bone at the fracture. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early time period when standard radiographic information of the fracture site is not capable of discriminating the healing pathway due to the relative paucity of mineralized tissue. Manual assessment of fracture healing is also inadequate as a diagnostic tool in the early stages of healing. Therefore, there is a need for new technologies that provide diagnostic information as to the course of healing within the first 6 post-operative weeks, which would provide a significant impact on the clinical orthopaedic practice and treatment of problematic fractures. The present invention addresses this need.